CSF1R Antibodies

Macrophage colony-stimulating factor 1 receptor (CSF1R)

Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby has an important role in innate immunity and in inflammatory processes.

Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is needed for normal bone and tooth development. Required for normal male and female fertility, and also for normal development of milk ducts and acinar structures in the mammary gland during pregnancy.

Gene Information

Human
Gene Name:	CSF1R
Uniprot:	P07333
Entrez:	1436

Family

Belongs to:
protein kinase superfamily

Alternative Names

CD115 antigen; CD115; c-fms; colony stimulating factor 1 receptor; CSF1R; CSF-1-R; CSFR; EC 2.7.10.1; FMS proto-oncogene; FMSFIM2; macrophage colony stimulating factor I receptor; macrophage colony-stimulating factor 1 receptor; McDonough feline sarcoma viral (v-fms) oncogene homolog; M-CSF R; MCSFR; M-CSFR; Proto-oncogene c-Fms

Molecular Weight

Mass (kDA):
107.984 kDA

Genomic Context

Human
Location:	5q32
Sequence:	5; NC_000005.10 (150053291..150113372, complement)

Tissue Specificity

Expressed in bone marrow and in differentiated blood mononuclear cells.

Subcellular Localizations

Cell membrane; Single-pass type I membrane protein.

Diseases

• Neoplasms
• Leukemia
• Malignant Neoplasms
• Myeloid Leukemia
• Leukemia, Myelocytic, Acute
• Dysmyelopoietic Syndromes
• Loss Of Chromosome 5q
• Inflammation
• Chromosomal Translocation
• Cell Transformation, Neoplastic
• Myelodysplastic Syndrome With Isolated Del(5q)
• Carcinoma

• Giant Cell Tumors
• Pigmented Villonodular Synovitis
• Leukoencephalopathies
• Synovitis
• Leukemogenesis
• Neoplasm Metastasis

Interacting Proteins

• CSF1

Pathways

• Pathogenesis
• Cell Proliferation
• Localization
• Angiogenesis
• Immune Response
• Cell Cycle
• Macrophage Differentiation
• Cell Growth
• Bone Resorption
• Osteoclast Differentiation
• Contact Inhibition
• Cell Development
• Cell Death

• Cell Adhesion
• Cell Differentiation
• Chromatin Remodeling
• Dna Methylation
• Macrophage Activation
• Phagocytosis
• Methylation

PTMs

• Phosphorylation
• Cleavage

• Dephosphorylation
• Methylation

• Prenylation

Research Areas

• Protein Kinase

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/CSF1R

Best Uses Of The CSF1R Marker From Boster Bio

Boster Bio's antibodies are known for their high affinity and specificity. Boster Bio tests its antibodies on several platforms to ensure that they are specific and high quality. They also reward their initial reviewers with product credits, and reward every scientist worldwide for their hard work. Boster is the best company to reach out to if you are looking to find the most effective uses for the CSF1R marker.

CSF1R-targeted therapies could be beneficial to MSS CRC patients.

Although immunotherapy for MSS CRC has shown positive results in a small subgroup of patients, a recent study suggests that patients suffering from mCRC also benefit from blocking the immune checkpoint. The study included patients who had or did not have any mutations in the MMR-D protein. The principal co-endpoints were 40% immune-related ORR at 20 weeks and 78% progression-free mortality at 20 weeks. The response rates of patients without CRC and those with MMR-D tumors were comparable.

Another study investigated the effects of fruquintinib (a novel oral TKI) on mCRC patients. It demonstrated a significant improvement in median OS and PFS in comparison to conventional therapies. The CSF1R-targeted therapy proved to be beneficial for patients suffering from MSS CRC. However the results of this trial are still insufficient.

Pexidartinib is yet another treatment for MSS CRC. It is a CSF1R antagonist currently being investigated in combination with cetuximab. Cetuximab which is an anti-EGFR inhibitor has been proven to infiltrate T cells from the intratumoral region in patients with metastatic colon cancer treated with cetuximab.

There are many ongoing trials that are testing the effectiveness of trastuzumab with irinotecan or cetuximab. Other studies are evaluating the efficacy of trastuzumab and tucatinib (ONT-380) in patients with advanced CRC. These clinical trials are the first to combine two CSF1R-targeted therapies.

Two phase I clinical trials demonstrated that Pembrolizumazumazumazuma is safe and efficient. It inhibits the CSF-1 receptor. It is an enzyme that transforms macrophages into tumor suppressors. Although this may seem like an unimaginative approach to an effective treatment for cancer, there are still many reasons why you should be positive. The targeted therapies may have a minimal adverse effect on MSS CRC patients, provided they are considered safe.

There is still some evidence that suggests CSF1R may still be useful even though there is not consensus on its role. It is rare to find the fusion of this gene via liquid biopsy. Furthermore, a small proportion of MSS CRC patients may benefit from targeted treatments. These data are encouraging, but further research is needed to determine if CSF1R-targeted therapies can still be beneficial to MSS CRC patients.

Multiple solid tumors have been treated through immunotherapy, which is now a more popular treatment. Patients with MSS CRC have shown long-term and long-lasting results from immunotherapy. Two PD1-blocking antibody that target the PD1 receptor were recently approved by the regulatory authorities. The antibodies have been shown to be effective in patients with metastatic MSS CRC.

The new immunotherapy is currently being evaluated in a phase II biomarker-driven umbrella trial in Korea. Combining this drug with chemotherapy has proven to have an ORR and PFS that are higher than placebo. The current study involves 33 patients. It will determine if the combination is effective in treating MSS CRC. The study will also evaluate its efficacy in treating patients suffering from GC.

CSF1R is a key player in the tyrosine-phosphorylation process SHC

We have previously identified a gene known as CSF1R that stimulates tyrosine-phosphorylation in SHC1/ INPP5D SHIP-1. The gene is crucial for the homeostasis of T cells in both human and mouse models of IBD. We are now able to investigate the potential therapeutic potential of this gene in the treatment of IBD.

In addition, a new study showed that a fusion transcript of two genes containing the SHIP1 protein was formed when sequence reads linked exon 25 in INPP5D to exon 2 of ATG16L1. This led to a truncated SHIP1 protein that has an molecular mass of 112. kDa and a predicted catalytic domain of three NPXY domains. The protein, whose sequence is still under investigation, may interact with other SH3-domain-containing proteins.

The peptide synthesized was created to mimic the human MCSF Receptor (955-972aa), which differs from the mouse and rat sequences by one amino acid. In addition, it was isolated from red blood cells with an anti-mouse anti-CD3 antibody and PerCP-Cy5.5 conjugated anti-NK1.1 antibodies. The samples were then washed using PBS-0.2 percent TritonX. They were then stained with FITC-conjugated anti CD4. The sections were then placed on coverslips. Images were captured after washing them with PBS.

Ship1 is a significant target for tyrosine-phosphatases as it acts as an adaptor protein for SHc and Grb2. EPO stimulates tyrosine phosphorylation in Ship1 by attracting it to EPO-R. EPO-R mutants also show incredible redundancy in recruiting Ship1.

The expression patterns of the genes associated with Inpp5D in human brains and mouse brains were examined. Inpp5D inhibition resulted in an increase in the spatially constrained microglia. Inducible CSF1R promotes the tyrosine-phosphorylation SHC1/INPP5D/SHIP-1.

We identified the protein as a potential target for tyrosine-phosphorylation with CSF1R inhibitor. This inhibitor also blocks SHC1 and INPP5D/SHIP-1 by encouraging tyrosine phosphorylation. This gene regulates neuronal cell differentiation and growth.

We utilized genomic DNA extracted from whole blood using the QIAamp DNA Blood Mini Kit. For spatial transcriptomics, hemibrains had to be cut at ten mm, mounted on glass slides, and then fixed in 4% paraformaldehyde over 15 min at 4 degC. After drying the sections, they were stained with methoxy-XO4(MTX), by placing them in 50 percent EtOH for 2 minutes and 70 percent EtOH for another 30 seconds.

In Alzheimer's disease, CSF1R is expressed in microglia. CSF1R1 stimulates microglia. It also plays a role in mammary gland development. CSF1R is a key factor in the tyrosine-phosphorylation of SHC and INPP5D/SHIP-1. It also has numerous therapeutic uses.

We utilized the edgeR gene expression program to conduct an analysis of multidimensional scaling. Using sum of counts, a multidimensional scaling (MDS) plot was generated. The plot shows the relative enrichment of genes in different data clusters. EdgeR's clustering software was used to identify distinct DEGs and excluding genes that overlap.

CSF1R-targeted therapies may boost ongoing immune-to-tumor response

Antibodies against the CSF1R tyrosine Kinase have been made available for the treatment of cancers that are solid. These compounds were shown to boost the anti-tumor immune response of cancer patients and to decrease the survival of tumor cells in preclinical research. The high sensitivity and specificity of CSF1R inhibitors suggest that they may have the potential to enhance the anti-tumor immune response of patients suffering from refractory solid malignancies.

The preliminary data show that CSF1R inhibitor sensitivity is positively correlated with CSF1R ligand levels in primary AML patient samples. The results of further studies are needed to verify the presence of CSF1R-targeted therapies and to determine the importance of this connection. These results suggest that CSF1R-targeted therapies may increase the anti-tumor immune response in cancer patients.

Another intriguing study examined the role of IL-2 immunotherapy for stimulating a tumor-specific immune response. Combining CD40 antibodies with immunotherapy enhanced tumor-specific T cell (TCR) responses, and the combined therapy resulted in complete regression of metastatic tumors. A combination of CD40 antibodies and immunotherapy resulted in an increase in the survival rate of T cells in patients with metastatic PDAC.

Combining chemotherapy with CSF1R-targeted therapies is also a promising treatment option. This treatment could enhance the effectiveness of immune responses for patients who have been unresponsive to immunotherapy. In a recent study the combination of CSF1R-targeted immune therapy with immunotherapy resulted in regression of established orthotopic tumors in an experimental PDAC model. Further, the combined treatment decreased the amount of tumor-infiltrating TILs and macrophages.

The adoption of autologous TILs was the first method to boost the anti-tumor immune system. The procedure of identifying and extending cells from patients isn't without its limitations. In recent years, engineered T-cell strategies have been employed to enhance the anti-tumor immune response. One of these strategies is CAR-T cell transplantation (CART) using genetically engineered lymphocytes expressing antitumor TCRs.

Another promising therapy is combining CSF1R inhibitors with chemotherapy. It has been shown that it can increase TIL antitumor function, as well as increase granzyme B and IFN-g levels. This can improve overall survival. The combination is currently being evaluated in a phase I trial. It is currently the best method of fighting pancreatic cancer. It may even enhance the effectiveness of chemotherapy.

It is essential to develop an innovative approach to treat cancer. Acquired resistance is an important aspect in this regards. The potential for CSF1R targeted therapies to improve anti-tumor immunity response is far from being realized. Therefore, further research is necessary. In the next section, we will review the advantages of CSF1R targeted therapies.